Experimental Procedures for Barbier Reactions

In general, not only experimental skill and experience are required to carry out a planned organic synthesis. Some precautions have to be taken and some conditions have to be fulfilled-the so-called tricks of the specialist-in order to obtain the best possible results. 

Among the earliest reports of such specialist s tricks to promote a smooth procedure in which an organo halide and a metal were involved, was Pebal s publication on the preparation of diethylzinc in 1861 [1] (see Sect. 1.2.2, p. 3). For the reaction of iodoethane with zinc in diethyl ether he used zinc that had first been etched ( angeatz ) with sulfuric acid, washed and carefully dried. 

Furthermore the diethyl ether was first made completely anhydrous with anhydrous phosphoric acid . 

That the trick did not always work as indicated in the report may probably be concluded from the fact that, one year later, Rieth and Beilstein [2] recommended the use of a 4 1 zinc/sodium alloy for the same reaction. 

Many of the readers of this monograph, if not all of them may recognize the starting problems in routine organometallic reactions. Such problems evidently were encountered from the very beginning of organometallic chemistry. 

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To better compare modern protocols for the Reformatsky reactions, hereinafter discussed in this section, it is interesting to read, as an example, the experimental procedure reported by R. B. Woodward and coworkers in 1956 for the synthesis of the Lysergic acid precursor 3 (equation 2)14. The procedure adopted was a Barbier-like protocol, involving the addition of Zn and of methyl bromoacetate (la) in three portions to a solution of 2 in hot benzene. 

This practical chapter in a monograph on the Barbier reaction will deal with some experimental procedures and such special conditions-mainly with regard to the activation of the metal - required for the optimal execution of Barbier and Barbier-type reactions. 

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